Exosome-like silica nanoparticles: a novel ultrasound contrast agent for stem cell imaging

被引:95
作者
Chen, Fang [1 ,2 ]
Ma, Ming [3 ]
Wang, Junxin [1 ]
Wang, Fang [4 ]
Chern, Shi-Xiong [3 ]
Zhao, Eric Ruike [1 ]
Jhunjhunwala, Anamik [5 ]
Darmadi, Sean [1 ]
Chen, Hangrong [3 ]
Jokerst, Jesse V. [1 ,2 ]
机构
[1] Univ Calif San Diego, Dept NanoEngn, 9500 Gilman Dr, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Mat Sci & Engn Program, 9500 Gilman Dr, La Jolla, CA 92093 USA
[3] Chinese Acad Sci, Shanghai Inst Ceram, State Key Lab High Performance Ceram & Superfine, Shanghai 200050, Peoples R China
[4] Univ Sci & Technol Beijing, Res Ctr Bioengn & Sensing Technol, Beijing 100083, Peoples R China
[5] Univ Calif San Diego, Dept Bioengn, 9500 Gilman Dr, La Jolla, CA 92093 USA
基金
中国国家自然科学基金;
关键词
DRUG-DELIVERY; SURVIVAL; THERAPY; NANOSPHERES;
D O I
10.1039/c6nr08177k
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Ultrasound is critical in many areas of medicine including obstetrics, oncology, and cardiology with emerging applications in regenerative medicine. However, one critical limitation of ultrasound is the low contrast of target tissue over background. Here, we describe a novel cup-shaped silica nanoparticle that is reminiscent of exosomes and that has significant ultrasound impedance mismatch for labelling stem cells for regenerative medicine imaging. These exosome-like silica nanoparticles (ELS) were created through emulsion templating and the silica precursors bis(triethoxysilyl) ethane (BTSE) and bis(3-tri-methoxysilyl-propyl) amine (TSPA). We found that 40% TSPA resulted in the exosome like-morphology and a positive charge suitable for labelling mesenchymal stem cells. We then compared this novel structure to other silica structures used in ultrasound including Stober silica nanoparticles (SSN), MCM-41 mesoporous silica nanoparticles (MSN), and mesocellular foam silica nanoparticles (MCF) and found that the ELS offered enhanced stem cell signal due to its positive charge to facilitate cell uptake as well as inherently increased echogenicity. The in vivo detection limits were <500 cells with no detectable toxicity at the concentrations used for labelling. This novel structure may eventually find utility in applications beyond imaging requiring an exosome-like shape including drug delivery.
引用
收藏
页码:402 / 411
页数:10
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